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Nanotechnology: The ultimate tools for medicine ? PD Dr.med Patrick Hunziker Div. of Intensive Care Medicine & Cardiology Physics.

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Presentation on theme: "Nanotechnology: The ultimate tools for medicine ? PD Dr.med Patrick Hunziker Div. of Intensive Care Medicine & Cardiology Physics."— Presentation transcript:

1 Nanotechnology: The ultimate tools for medicine ? PD Dr.med Patrick Hunziker Patrick.Hunziker@unibas.ch Div. of Intensive Care Medicine & Cardiology Physics in Medicine Research Group University Hospital Basel

2 What happened to the Bayer shares ?

3 The promise of Nano-Medicine Eric Drexler, 1986

4 Current impact of nanotech on medicine: Medline impact: 117 / 11’000’000 citations with “nanotechnology” (mostly “science fiction” articles) compare: 120’000 citations with “catheter” => in medicine, nanotechnology is in its infancy !

5 List of all original papers clinical application of nanotechnology in medicine :

6 body dimensions of life - dimensions of medicine organs blood vessels neurons most cells nucleus cell organelles supramol. assemblies proteins small molecules m dm cm mm mm nm m dm cm mm mm nm body components atoms in vivo diagnosis human eye stethoscope X-ray ultrasound catheters MRI ( only blood cells:microscopes ) biochemical tests artificial hips scalpel catheters therapeutic radiation treatment drugs “there is plenty of room at the bottom”

7 Medical treatment today: a fundamental size mismatch... bodyorgans blood vessels neurons most cells nucleus cell organelles supramol. assemblies proteins small molecules m dm cm mm mm nm m dm cm mm mm nm body components atoms disease starts here artificial hips scalpel catheters therapeutic radiation your doctor’s watchmaker tool drugs your doctor is watering flowers..

8 Where all the action is: the cell ! nucleus: genome, gene expression cytoplasm: metabolism mitochondria mRNA ribosomes proteins fibrils vesicles endoplasmatic reticulum membrane proteins receptors channels

9 Nanotechnology in medicine: What are the targets ?

10 Watering flowers or flooding the neighburhood ? treating atherosclerosis with lipid lowering drugs arteriosclerosis: - begins at the cell -> focal lesions in the arteries - leads to myocardial infarction and stroke arterial plaque some lipid lowering drugs: effects on plaques can save lifes effects on immune system effects on liver muscles: can lead to cell death can endanger human life can endanger large companies

11 The bulldozer approach to atherosclerosis

12 Using a bulldozer for watchmaking ? the example of coronary artery disease Cells begin to accumulate cholesterol altered micromechanics inflammation of the arteriosclerotic plaque reactive molecules altered membrane protein expression cytokines heat vessel narrowing plaque rupture myocardial infarctionstroke angina

13 Watering flowers or flooding the neighburhood ? Treatment of cancer anti-cancer drugs: typically kill rapidly growing cells kill rapidly growing cancer cells may save human lifes may not kill slowly growing cancer cells cancer may recur kill normal, rapidly growing cells -intestine -> vomiting -blood cells -> anemia -immune system ->infections may endanger life cancer: - starts as a single cell -is a focal disease

14 Medical diagnosis & treatment tomorrow: improve current technology body organs blood vessels neurons most cells nucleus cell organelles supramol. assemblies proteins small molecules m dm cm mm mm nm atoms Better materials for prostheses, stents etc: strenght, durability, biocompatibility Enlarge catheter-based measurement toolbox Biochemical tests: more sensitive/specific faster bedside/point of care array of parameters less expensive

15 Medical diagnosis tomorrow: break completely new ground ! body organs blood vessels neurons most cells nucleus cell organelles supramol. assemblies proteins small molecules m dm cm mm mm nm atoms in vivo small scale disease characterisation in vivo single cell probes in vivo cell nucleus probes in vivo probes for cell organelles in vivo probing of fibrous structures in vivo membrane protein monitoring in vivo biochemical monitoring

16 Medical treatment tomorrow: break completely new ground ! body organs blood vessels neurons most cells nucleus cell organelles supramol. assemblies proteins small molecules m dm cm mm mm nm atoms -targeted drug delivery -nanomechanical interventions - to specific locations - to specific tissues - to specific cells - based on sensor information e.g. - kill cancer cells directly - repair cellular substrate of atherosclerosis early - find/treat infections locally - directed somatic gene therapy - attack Alzheimer’s disease

17 Point of care diagnosis: immunological array testing Bernard, Michel & al, IBM Rüschlikon 8/01 micromosaic immunoassays applied to clinical inflammation markers M.Wolf, Kantonsspital Basel/IBM Rüschlikon8/01 10  m

18 Point of care diagnosis: nanomechanical olfactory sensors Baller, Lang, Gerber & al, IBM /Uni BaselArntz, IBM /Uni Basel /Kantonsspital Basel

19 Erased due to publication restrictions of novel technology

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21 Nanotechnology in action: observing disease processes involving fibrils C. Goldsbury, J. Kistler, U. Aebi et al, J. Mol. Biol. 285, 33 (1999) growth of beta-amyloid (->Alzheimer !) visualized by AFM

22 Gene chips: a promizing target for nanotech www.clontech.com a gene microarray featuring 8000 individual human cDNAs The human genome project: man>: ~ 40’000 genes -> measure activation of each (mRNA) -> no more than 40’000 enzymes -> all biologically relevant substance are substrates of these enzymes measurable

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24 Drug delivery devices Sensor driven drug application - e.g. insulin treatment in diabetics site-specific drug application - e.g. selectively targeting cancer cells with anticancer drugs

25 Single cell needles/syringes nondestructive monitoring of cell metabolism drug delivery device “closed loop therapy” cell gene therapy based on sensor info

26 Nanotubes in Medicine Erased due to publication restrictions of novel technology

27 Topics for nanomaterials in medicine Biocompatibility Fundamentals of self-assembly Improved mechanical characteristics Drug releasing materials Biodegradable materials

28 cell specific surface molecules The single cell as treatment target: Learn from creation ! virus specific protein T Lymphocyte nucleus “lethal kiss”

29 Steps toward single cell treatment cell specific surface molecules virus specific protein nucleus sensor unit wiring catheter effector unit

30 Steps toward single cell treatment cell specific surface molecules virus specific protein nucleus sensor unit effector unit power, logic Nano-Robot Heat production anaerobic metabolism lactate production pH decrease

31 Biologic examples for simple autonomous units key capabilitynot capable ofenergy production red blood cells: gas transport pH buffer glycolysis self replication mobility protein synthesis blood platelet: shape change, degranulate aggregate upon signal glycolysis self replication protein synthesis virus:none“cristal” with software can dock to/invade cells. metabolism mobility self replication neurons:electrical response to electrical/chemical stimuli complex Lymphocytes:recognize self and non-self specific response complex

32 Wishlist for single cell sensors in the nanoscale presence/concentration of proteins presence of mRNA Receptor binding phenomena tip-based spectroscopy (optical, NMR) electric potential heat production pH Redox potential gas pressures NO concentration concentration of small biomolecules (lactate, cations, cAMP..)

33 potential problems of nanotechnology in medicine Number of cells in the body ~10 12 -> for biological impact: treat >10 8 cells => new manufacturing methods needed Will the immune system recognize and eliminate nanoparticles ? (immune response, biocompatibility, nano-mimickry) Influenza viruses kills 10 Mio people during world war I Computer virus shoots down millions of PC’s worldwide in y 2000 -> Autonomous, self-replicating nano-agents: a danger for the future ?

34 Nanoviruses “A synthetic nanovirus is 5 years away” C.Hutchinson, AAAS 2001 BBC News

35 Foresight Guidelines on Molecular Nanotechnology MNT (molecular nanotechnology) device designs should incorporate provisions for built-in safety mechanisms, such as: 1) absolute dependence on a single artificial fuel source or artificial "vitamins" that don't exist in any natural environment; 2) making devices that are dependent on broadcast transmissions for replication or in some cases operation; 3) routing control signal paths throughout a device, so that subassemblies do not function independently; 4) programming termination dates into devices, and 5) other innovations in laboratory or device safety technology developed specifically to address the potential dangers of MNT. Further research is needed on MNT risk management, as well as the theory, mechanisms, and experimental designs for built-in safeguard systems. Version 3.7: June 4, 2000

36 Ecophagy Some Limits to Global Ecophagy by Biovorous Nanoreplicators, with Public Policy Recommendations Robert A. Freitas Jr. http://www.foresight.org/NanoRev/ “Replication time  of biovorous nanoreplicators is limited by substrate availability: t >12’000 sec.” “Early detection is key to effective defense”

37 Nanotech in Medicine: Ethical Questions Breaking new ground: Creation of autonomous (“living”) agents Blurring of frontiers between “beings” and “things” -> “allowed to mankind” ? -> “acceptable to society” ? -> controllable at long term ? -> potential for infectious spread of self-replicating machines ? Gradual improvement of current tools/techniques -> probably acceptable to everybody -> which parts of mankind will profit ?

38 Nanotech in Medicine: Outlook 2) Nanotechnology will break new ground in - monitoring technology in critically ill patients - in vivo diagnosis within the body - allowing single cell diagnostics, monitoring & treatment in the body - will outperform the impact of gene therapy 1) Nanotechnology will -revolutionize medical laboratory diagnosis within a few years 3) Nanotechnology will - produce simple prototypes of nanorobots within a decade, thus - blur the frontier between “beings” and “things” -> an array of ethical question will be raised -> to be addressed early

39 Thanks to The physicists for inventing nanotech Prof. Pfisterer and Prof. Marsch for encouragement & support Everybody in the Nano NCCR, esp Prof. Guentherodt for their great collaboration with that strange species of “medical doctor interested in physics” My wife and children for the lonely hours due to nanomedicine


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